Reproductive Biology and Endocrinology | |
The relationship between polymorphisms in the promoter region of Tim-3 and unexplained recurrent spontaneous abortion in Han Chinese women | |
Min Zhu1  Haiyan Lv1  Lilong Fan1  Chiting Yuan1  Congcheng Fang1  Baojin Zeng2  Dun Hong1  Chen Wang2  Yang Shen1  | |
[1] The Public Laboratory, Taizhou Hospital of Zhejiang Province, Wenzhou Medical College, Linhai, Zhejiang 317000, China;The department of obstetrics and gynaecology, Taizhou Hospital of Zhejiang Province, Wenzhou Medical College, Linhai, Zhejiang 317000, China | |
关键词: Cytokines; Gene polymorphism; Tim-3; Unexplained recurrent spontaneous abortion; | |
Others : 809881 DOI : 10.1186/1477-7827-11-104 |
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received in 2013-08-16, accepted in 2013-11-07, 发布年份 2013 | |
【 摘 要 】
Background
Recurrent spontaneous abortion (RSA) refers to 2 or more consecutive pregnancy losses, and RSA with unknown causes is called unexplained recurrent spontaneous abortion (URSA). Tim-3, a subtype of the T-cell immunoglobulin domain and mucin domain (Tim) protein family, might be an important regulatory molecule that plays a pivotal role in URSA, which might be triggered mostly by Th1/Th2 immune deviation. To understand the etiology and pathogenesis of URSA in Han Chinese women, we investigated the association between polymorphisms of rs10053538 and rs10515746 in the promoter of Tim-3 and the risk of URSA in Han Chinese women.
Methods
One hundred and forty-eight women with RSA resulting in still birth were enrolled in the URSA group. We performed tests to rule out congenital reproductive system malformation, reproductive system tumor, endocrine dyscrasia, and chromosome abnormalities. One hundred and fifty-three women with normal pregnancy leading to live birth were selected at random to comprise the control group. All women included in this study were genetically unrelated Han Chinese women. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele-specific polymerase chain reaction (AS-PCR) were used to determine polymorphisms of rs10053538 and rs10515746, respectively, in all subjects. PCR products were chosen at random for sequencing.
Results
No significant statistical difference was found between the distribution frequency of the GT + TT genotype and T allele on the rs10053538 locus in the URSA group or the control group (10.1% vs. 11.8%, Chi(2) = 0.205, P = 0.651; 5.1% vs. 6.5%, Chi(2) = 0.592, P = 0.441; respectively). Neither was there a significant difference between the distribution frequency of the GT + TT genotype and T allele on the rs10515746 locus in the groups (6.8% vs. 3.9%, Chi(2)1.201, P = 0.273; 3.4% vs. 2.0%, Chi(2) = 1.169, P = 0.280; respectively).
Conclusions
The present study suggested that these polymorphisms of rs10053538 or rs10515746 in the Tim-3 promoter may not be associated with URSA in Han Chinese women.
【 授权许可】
2013 Shen et al.; licensee BioMed Central Ltd.
【 预 览 】
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Figure 1. | 33KB | Image | download |
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【 参考文献 】
- [1]Jahaninejad T, Ghasemi N, Kalantar SM, Sheikhha MH, Pashaiefar H: StuI polymorphism on the androgen receptor gene is associated with recurrent spontaneous abortion. J Assist Reprod Genet 2013, 30:437-440.
- [2]Wilczynski JR, Radwan P, Tchorzewski H, Banasik M: Immunotherapy of patients with recurrent spontaneous miscarriage and idiopathic infertility: does the immunization-dependent Th2 cytokine overbalance really matter? Arch Immunol Ther Exp (Warsz) 2012, 60:151-160.
- [3]Tafuri A, Alferink J, Moller P, Hammerling GJ, Arnold B: T cell awareness of paternal alloantigens during pregnancy. Science 1995, 270:630-633.
- [4]Yamada H, Morikawa M, Furuta I, Kato EH, Shimada S, Iwabuchi K, Minakami H: Intravenous immunoglobulin treatment in women with recurrent abortions: increased cytokine levels and reduced Th1/Th2 lymphocyte ratio in peripheral blood. Am J Reprod Immunol 2003, 49:84-89.
- [5]Chaouat G: The Th1/Th2 paradigm: still important in pregnancy? Semin Immunopathol 2007, 29:95-113.
- [6]Krechetova LV, Nikolaeva MA, Van’ko LV, Ziganshina MM, Golubeva EL, Stepanova EO, Sukhikh GT: Optimal detection of serum antipaternal antileukocytic antibodies after injection of allogenic lymphocytes in women with habitual abortions. Bull Exp Biol Med 2012, 153:726-729.
- [7]Chae SC, Song JH, Pounsambath P, Yuan HY, Lee JH, Kim JJ, Lee YC, Chung HT: Molecular variations in Th1-specific cell surface gene Tim-3. Exp Mol Med 2004, 36:274-278.
- [8]Rodriguez-Manzanet R, DeKruyff R, Kuchroo VK, Umetsu DT: The costimulatory role of TIM molecules. Immunol Rev 2009, 229:259-270.
- [9]Popovici RM, Krause MS, Germeyer A, Strowitzki T, von Wolff M: Galectin-9: a new endometrial epithelial marker for the mid- and late-secretory and decidual phases in humans. J Clin Endocrinol Metab 2005, 90:6170-6176.
- [10]Ndhlovu LC, Lopez-Verges S, Barbour JD, Jones RB, Jha AR, Long BR, Schoeffler EC, Fujita T, Nixon DF, Lanier LL: Tim-3 marks human natural killer cell maturation and suppresses cell-mediated cytotoxicity. Blood 2012, 119:3734-3743.
- [11]McIntire JJ, Umetsu SE, Macaubas C, Hoyte EG, Cinnioglu C, Cavalli-Sforza LL, Barsh GS, Hallmayer JF, Underhill PA, Risch NJ, et al.: Immunology: hepatitis A virus link to atopic disease. Nature 2003, 425:576.
- [12]Sabatos CA, Chakravarti S, Cha E, Schubart A, Sanchez-Fueyo A, Zheng XX, Coyle AJ, Strom TB, Freeman GJ, Kuchroo VK: Interaction of Tim-3 and Tim-3 ligand regulates T helper type 1 responses and induction of peripheral tolerance. Nat Immunol 2003, 4:1102-1110.
- [13]Freeman GJ, Casasnovas JM, Umetsu DT, DeKruyff RH: TIM genes: a family of cell surface phosphatidylserine receptors that regulate innate and adaptive immunity. Immunol Rev 2010, 235:172-189.
- [14]Monney L, Sabatos CA, Gaglia JL, Ryu A, Waldner H, Chernova T, Manning S, Greenfield EA, Coyle AJ, Sobel RA, et al.: Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease. Nature 2002, 415:536-541.
- [15]Cai C, Wang L, Wu Z, Li M, Chen W, Sun Y: T-cell immunoglobulin- and mucin-domain-containing molecule 3 gene polymorphisms and renal cell carcinoma. DNA Cell Biol 2012, 31:1285-1289.
- [16]Tong D, Zhou Y, Chen W, Deng Y, Li L, Jia Z, Qi D: T cell immunoglobulin- and mucin-domain-containing molecule 3 gene polymorphisms and susceptibility to pancreatic cancer. Mol Biol Rep 2012, 39:9941-9946.
- [17]Xu J, Yang Y, Liu X, Wang Y: The -1541 C > T and +4259 G > T of TIM-3 polymorphisms are associated with rheumatoid arthritis susceptibility in a Chinese Hui population. Int J Immunogenet 2011, 38:513-518.
- [18]Graves PE, Siroux V, Guerra S, Klimecki WT, Martinez FD: Association of atopy and eczema with polymorphisms in T-cell immunoglobulin domain and mucin domain-IL-2-inducible T-cell kinase gene cluster in chromosome 5 q 33. J Allergy Clin Immunol 2005, 116:650-656.